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Full design automation of multi-state RNA devices to program gene expression using energy-based optimization

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Full design automation of multi-state RNA devices to program gene expression using energy-based optimization

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dc.contributor.author Rodrigo Tarrega, Guillermo es_ES
dc.contributor.author Landrain, Thomas E. es_ES
dc.contributor.author Majer, Eszter es_ES
dc.contributor.author Daros Arnau, Jose Antonio es_ES
dc.contributor.author Jaramillo, Alfonso es_ES
dc.date.accessioned 2016-01-13T10:30:54Z
dc.date.available 2016-01-13T10:30:54Z
dc.date.issued 2013-08
dc.identifier.issn 1553-734X
dc.identifier.uri http://hdl.handle.net/10251/59787
dc.description.abstract [EN] Small RNAs (sRNAs) can operate as regulatory agents to control protein expression by interaction with the 59 untranslated region of the mRNA. We have developed a physicochemical framework, relying on base pair interaction energies, to design multi-state sRNA devices by solving an optimization problem with an objective function accounting for the stability of the transition and final intermolecular states. Contrary to the analysis of the reaction kinetics of an ensemble of sRNAs, we solve the inverse problem of finding sequences satisfying targeted reactions. We show here that our objective function correlates well with measured riboregulatory activity of a set of mutants. This has enabled the application of the methodology for an extended design of RNA devices with specified behavior, assuming different molecular interaction models based on Watson-Crick interaction. We designed several YES, NOT, AND, and OR logic gates, including the design of combinatorial riboregulators. In sum, our de novo approach provides a new paradigm in synthetic biology to design molecular interaction mechanisms facilitating future high-throughput functional sRNA design. es_ES
dc.description.sponsorship Work supported by the grants FP7-ICT-043338 (BACTOCOM) to AJ, and BIO2011-26741 (Ministerio de Economia y Competitividad, Spain) to JAD. GR is supported by an EMBO long-term fellowship co-funded by Marie Curie actions (ALTF-1177-2011), and TEL by a PhD fellowship from the AXA Research Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. en_EN
dc.language Inglés es_ES
dc.publisher Public Library of Science es_ES
dc.relation.ispartof PLoS Computational Biology es_ES
dc.rights Reconocimiento (by) es_ES
dc.subject Agents to control protein es_ES
dc.subject Small RNAs (sRNAs) es_ES
dc.title Full design automation of multi-state RNA devices to program gene expression using energy-based optimization es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1371/journal.pcbi.1003172
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/043338/EU/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MICINN//BIO2011-26741/ES/PATOGENOS DE RNA DE PLANTAS: INTERACCION CON EL HUESPED Y DESARROLLO DE HERRAMIENTAS BIOTECNOLOGICAS/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/EC/Marie Skłodowska-Curie Actions/ALTF-1177-2011/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Instituto Universitario Mixto de Biología Molecular y Celular de Plantas - Institut Universitari Mixt de Biologia Molecular i Cel·lular de Plantes es_ES
dc.description.bibliographicCitation Rodrigo Tarrega, G.; Landrain, TE.; Majer, E.; Daros Arnau, JA.; Jaramillo, A. (2013). Full design automation of multi-state RNA devices to program gene expression using energy-based optimization. PLoS Computational Biology. 9(8):1003172-1003172. https://doi.org/10.1371/journal.pcbi.1003172 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion http://dx.doi.org/10.1371/journal.pcbi.1003172 es_ES
dc.description.upvformatpinicio 1003172 es_ES
dc.description.upvformatpfin 1003172 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 9 es_ES
dc.description.issue 8 es_ES
dc.relation.senia 258245 es_ES
dc.identifier.eissn 1553-7358
dc.identifier.pmid 23935479 en_EN
dc.identifier.pmcid PMC3731219 en_EN
dc.contributor.funder European Commission
dc.contributor.funder Ministerio de Ciencia e Innovación es_ES
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